(135f) One-Step Regioselective Synthesis of Clindamycin Palmitate By Immobilized Lipase | AIChE

(135f) One-Step Regioselective Synthesis of Clindamycin Palmitate By Immobilized Lipase


Li, Z. - Presenter, Tsinghua University
Ge, J., Tsinghua University
Liu, Z., Key Lab of Industrial Biocatalysis, Ministry of Education, Tsinghua University

Clindamycin is an established antibiotic with proven effectiveness against Gram-positive organisms and Gram-negative anaerobes and thus has been widely applied to treat diseases including infections of the respiratory tract, skin and soft-tissue. Clindamycin could be used as a first-line treatment option for the methicillin-resistant Staphylococcus aureus (MRSA).

However, the synthesis of clindamycin palmitate involves laborious steps of protection and deprotection and gives an overall yield below 50%. Here we report the first example of the one-step synthesis of clindamycin palmitate with high regioselectivity using immobilized Candida antarctica lipase B (Novozym 435) as the catalyst. The lipase catalyzed synthesis reached a conversion above 90% in 12 hours in an organic solvent. Characterized by 1H and 13C NMR, DEPT, HMQC, ESI-MS and FT-IR spectra, a nearly 100% regioselective acylation was confirmed occurred at the 2-hydroxyl of clindamycin. The enzymatic acylation of clindamycin at the solvent-free condition catalyzed by Novozym 435 and other types of novel immobilized lipase such as the lipase-inorganic crystal hybrid nanoflower will also be introduced in this presentation. In summary, the one-step regioselective synthesis of clindamycin palmitate with a high yield (>90%) and a high regioselectivity (~100%) greatly simplifies the synthesis by excluding the group protection/deprotection procedures and downstream purifications, which makes this enzymatic process very attractive for the manufacturing of clindamycin ester derivatives in pharmaceutical industry.